Plasma concentrations and acceptability of mexiletine given by intramuscular injection in patients admitted to a...

We measured the plasma concentrations of mexiletine in patients admitted to a hospital coronary care unit after the intramuscular injection (IMI) of 200, 300, 400, and 500 mg mexiletine. Mexiletine was rapidly absorbed and concentrations greater than 0.75 microgram/ml were achieved in some patients within 5 min of the injection. The maximum mean plasma concentration increased with 200, 300, and 400 mg but was lower after 500 mg than after 400 mg. After 400 mg mexiletine, plasma concentrations greater than 0.75 microgram/ml were achieved in at least seven of nine patients from 15 min to 2 h after administration. There were no local reactions to 200, 300, or 400 mg mexiletine, but local pain and tenderness occurred in three of nine patients after 500 mg. It was decided that 400 mg mexiletine would probably be the desired dose for intramuscular administration. In 14 patients given mexiletine 400 mg by IMI followed at 2 and 12 h by 360 mg by mouth the plasma concentration was in the therapeutic range (0.75-2.0 micrograms/ml) from 15 min to 24 h in at least 64% of patients. In 12 healthy volunteers the IMI of 400 mg mexiletine increased total creatinine kinase (CK), aspartate amino-transferase, and lactate dehydrogenase enzymes but CK-MB, LDi, and LDii concentration or LDi/LDii ratio were not outside the normal range. These studies indicate that mexiletine can be safely given to patients by IMI and that therapeutic plasma concentrations are achieved.